Among other sample manipulations, blood separation is a routine process that is typically required in many analytic tests. Most commonly, separation is carried out in a centrifuge using a polymeric gel having a density (about 1.04) that is between the heavier cell-containing phase and the lighter serum-containing phase. Examples for separation devices that use intermediate density polymers are found in U.S. Pat. No. 3,647,070 where polymer spheres form the barrier layer, while U.S. Pat. No. 5,266,199 describes a tube-and-ball valve that controls separation of the serum from the cell-containing phase. However, such barriers are often either incomplete and tend to leak, or impracticable for various reasons.
Alternatively, relatively impervious silicone-containing barrier layers can be used in the serum separation as described in U.S. Pat. No. 3,780,935, and drug-impermeable separation polymers are described in EP 0 928 301 in which fluid polymers are used as a barrier layers. Similarly, U.S. Pat. No. 4,235,725 describes the use of polybutadiene plus filler material as a barrier forming material. Such barrier materials often provide at least some advantage, but typically fail to maintain the separation over a prolonged period. In still further known serum separation devices, high-density polymers can be employed for blood separation in which the density is adjusted to a desirable degree with a density reducing component as taught in EP 0 705 882. Such compositions are often highly compatible with blood, and often exhibit favorable viscosity. However, such barrier layers are often unstable over prolonged periods. Alternatively, the viscosity of the intermediate polymer may also be increased in the separator tube by photopolymerization before the tubes is used for collection and separation as described, for example, in U.S. Pat. No. 6,361,700 or U.S. Pat. No. 6,248,844. Once more, while such tubes often provide increased sample stability, the barrier layer is typically unstable over prolonged periods and will deteriorate upon freezing.
Still further known devices and methods are described in EP 0 520 185 using fatty acid amides admixed with a gel, and EP 0 744 026 in which a peripheral water swellable band is taught as a barrier forming means. U.S. Pat. No. 3,920,557 described use of beads coated with an adhesive to form a barrier layer between the serum and the cell containing phase, while U.S. Pat. No. 4,101,422 discloses copolyesters with specific molecular weight and viscosity as barrier-forming compositions. While such known compositions tend to maintain the separation over at least relatively short periods, the separation layers are often not sufficiently stable to allow reliable storage over several days or while frozen.
Therefore, while numerous compositions and methods for centrifugal serum separation are known in the art, all or almost all of them suffer from one or more disadvantages. Thus, there is still a need to provide improved composition and methods to improve serum separation devices.